Although recent data suggest that the nuclear regulatory protein, PPARalpha, interacts with long chain fatty acyl CoA (LCFACoA), it is unclear whether this represents high affinity binding that is physiologically significant. Little is known regarding the distribution of LCFA-CoA to the nucleus or factors that transport LCFA-CoA to the nucleus for regulating nuclear transcription. Liver cytoplasm is rich in high affinity LCFA-CoA binding proteins, fatty acid binding protein (L-FABP) >> acyl CoA binding protein (ACBP). Transcriptional activation of PPARalpha strongly upregulates L-FABP expression. These data led to the hypothesis that LCFA-CoA binding protein(s) regulate the distribution of LCFA-CoA to the nucleus for interaction with and regulation of PPARalpha transcriptional activity. The specific aims are to: Aim 1. Determine if PPARalpha binds LCFA-CoA with high affinity, in the physiological range of nuclear LCFA-CoA levels. Aim 2. Resolve whether L-FABP regulates LCFA-CoA distribution to the nucleus. Aim 3. Elucidate whether L-FABP directly interacts with PPARalpha in the nucleus.